The present invention relates to the treatment of ailments in humans and other mammals, and more particularly, to a method and apparatus for delivering pharmaceutical compounds and genes into the endothelial and other nearby cells of a patient.
In the above identified prior application there is disclosed a catheter device which is inserted into a selected blood vessel of a patient and advanced to a preselected location within the blood vessel where the endothelial cells on the inner wall of the vessel are to be treated. Once in place, the catheter device is expanded so that a plurality of axially extending, circumferentially spaced electrodes carried thereby are in contact with the inner wall of the blood vessel. A fluid medium is then infused into the blood vessel adjacent the electrodes via infusion ports communicating by supply lines from a conventional pump. A power pack connected to the electrodes is energized to apply a predetermined voltage pulse to the electrodes and generate electric fields of predetermined amplitude. This subjects the endothelial cells to electric fields of predetermined amplitude and duration in making the walls of the endothelial cells transiently permeable to permit therapeutic genes or drugs carried by the fluid medium to enter the endothelial cells without killing them.
Endothelial cells are in direct contact with the blood stream and cover almost one thousand square meters of the inner surface of the blood vessels of a human. The blood vessels extend throughout the body and closely adjacent to almost all tissue of the body. The invention of the parent application was developed primarily to treat damage to endothelial cells which has been linked to cardiovascular diseases such as arteriosclerosis and high blood pressure. Endothelial cell damage may result from surgical procedures such as heart transplantation and by balloon angioplasty and routing of the blood vessels with rotary and laser catheters. These procedures are frequently used to remove blockage in the coronary arteries, however, the resulting trauma and scarring to the lumen walls can lead to rapid return of fatty deposits and a recurrence of blockage. Our studies have indicated that genetic modification of the endothelial cells might correct the damage caused by surgical procedures and could reduce the rate of deposit of low density cholesterol before and after surgical procedures. Insertion of drugs directly into the cells also appears to be effective to alleviate problems associated with damage to these cells.
The blood vessels can also be used to transport genes and drugs to areas for treatment of tissue and cells in areas adjacent to the vessels. They can also be used to place field generating means adjacent the areas to be treated. We have developed methods and apparatus for combined iontophoresis and electroporation for delivery of genes and drugs via the blood vessels into endothelial and other adjacent cells in the body. Electroporation in combination with iontophoresis can be used with improved catheters of the present invention to provide improved and extended drug and gene therapy.
A problem with the prior device is that blood may continue to flow and carry away the therapeutic fluid medium before treatment is completed.
Therefore, it is desirable that means be available for confining the therapeutic fluid to the treated area during treatment.
It is also desirable that improved catheters for drug and gene delivery to cells and for electric field generation be available.
It is also desirable that improved methods for drug and gene delivery to cells and for electric field generation for iontophoresis and electroporation be available.